CN104755014A - Fibrescope for optical imaging of radiopharmaceuticals - Google Patents
Fibrescope for optical imaging of radiopharmaceuticals Download PDFInfo
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- CN104755014A CN104755014A CN201380041119.7A CN201380041119A CN104755014A CN 104755014 A CN104755014 A CN 104755014A CN 201380041119 A CN201380041119 A CN 201380041119A CN 104755014 A CN104755014 A CN 104755014A
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- image
- light
- illumination
- cherenkov
- fibrescope
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- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
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Abstract
An apparatus for optical imaging of Cerenkov luminescence from a region of interest on a subject subsequent to the subject receiving a dose of a radiopharmaceutical, the apparatus comprising: an imaging means capable of imaging Cerenkov photons; a fibrescope for transmitting light received at a distal end of the fibrescope to a proximal end of the fibrescope, the proximal end of the fibrescope being connected to the imaging means; and an optical shroud for surrounding the distal end of the fibrescope and for covering a region of interest.
Description
Technical field
The present invention relates to the method and apparatus of radiopharmaceutic optical imagery, particularly relate to the method and apparatus using fibrescope to carry out Cherenkov's luminescence imaging.
Background technology
Uncle's Lignum Rhamnellae people sieve (physics's Medical Biology (Phys Med Biol.) 2009) is observed, and some diagnostic radioactive drug used in nuclear medicine scan also can carry out optical imagery.Particularly, due to Cherenkov's luminescence phenomenon, the radiopharmaceutical of emission band charged particle (such as, α and beta-particle) produces detectable light.Cherenkov's photon is because the deceleration of charged particle in the tissue produces.The radiopharmaceutic optical imagery of charge particle emission is called Cherenkov's luminescence imaging (CLI).
CLI combines the advantage (comprising high-spatial and temporal resolution and low cost and form factor) of optical imagery, with the advantage of nuclear imaging (comprise radiopharmaceutic molecular specificity and widely commercial applicability).Optical imagery will be interpreted as and comprise ultraviolet near infrared ray wavelength.
Wish to use CLI under clinical setting, such as, in operation process, provide image to inform surgeon.At clinical setting, to implement the technological challenge of CLI be Cherenkov's frequency spectrum of conventional diagnostic radioactive isotope (particularly those are marked with the isotope of Value linear) is visible spectrum between 400-800 nanometer.Cherenkov's spectrum can be disturbed and arrange to background illumination in room.In addition, illumination can cause tissue automatically to send fluorescence in the visible spectrum, this fluorescence will with Cherenkov's signal overlap.
Therefore, under typical lighting condition, CLI is infeasible.All CLI application are so far all in pitch-dark room or do not have to carry out in the room of the interference of light.The method and system of CLI is described in: the application US 2011/0250128 of the people such as Huo Lan in 2011, mole imaging (Mol Imaging); The application US2012/0220870J of card Peng top grade people in 2012, nucleosome antibody medical science (J Nucl.Med); And Kothapalli etc. is published in the biomedical optical bulletin on June 1st, 2012, the 3rd volume, the article in No. 6.
Have also been proposed and use CLI to create 3D rendering by laminagraph device, as International Periodicals the 2011st volume of biomedical imaging, article ID is the description in the application WO 2012/083503 of the people such as the clock of 641618.WO 2012/083503 also describes the method for the three-dimensional imaging of Cherenkov's luminescence of the intensity distributions according to Cherenkov light.But these methods also need pitch-dark condition and are infeasible in clinical setting.
Summary of the invention
The present invention relates to and be a kind ofly actually used in the method and apparatus of clinical setting as the radiopharmaceutic optical imagery of operating room.
Particularly, inventor has determined to need to carry out imaging of tissue in original place to the open surgery position of patient or other clinical location.Such as, at the intra-operative from abnormal (such as carcinous) tissue of experimental subject removing, surgeon can carry out confirming that they have removed all abnormal structures and have been highly profitable before operation terminates; Common problem in such operation is that the marginal portion of abnormal tissue is left, once detect later, this must remove in performing the operation further.Therefore, a scheme of the present invention is to provide a kind of Cherenkov's of use luminescence imaging and checks at the tissue of clinical location as open surgery position, to check the imaging system that all abnormal structures (such as cancerous cell) have removed and method.
In first aspect, the invention provides the device of the optical imagery carrying out Cherenkov's luminescence after a kind of experimental subject accepts potion radiopharmaceutical from the area-of-interest experimental subject, this device comprises:
Imaging device, this imaging device can by the imaging of Cherenkov's photon;
Fibrescope, this fibrescope is used for the optical transport that received by the far-end at the fibrescope near-end to fibrescope, and the near-end of fibrescope is connected with imaging device; And
Light shield, this light shield for surround fibrescope far-end and for covering area-of-interest.
This light shield can pass through by (preferably fully) stop surround lighting at least substantially.This guard design becomes the surround lighting of 10 to 14 orders of magnitude of at least decaying in some embodiments.
The photon flux that the level of surround lighting that preferably imaging device receives produces should less than 10 of radiopharmaceutic photon flux times, otherwise may be difficult to maybe can not see Cherenkov's image.The photon flux that more preferably surround lighting produces is less than 10 times less than radiopharmaceutic flux.Typical radiopharmaceutic flux (such as F18) is 10
3with 10
4photon/s/sr/ centimetre
2.
By this way, when above guard shield is placed on area-of-interest, the skin being close to experimental subject with the feather edge of guard shield forms sealing around area-of-interest and (no matter is direct or uses extra sealing member, such as, as discussed below), light closed chamber is formed so that Cherenkov's imaging of this area-of-interest can be carried out.
This guard shield can be formed, successfully can carry out Cherenkov's imaging by any amount of suitable material of environmental light infiltration or the compositions of material of preventing to a certain extent.Can be such as rubbery light shading fabric, cellular rubber material as closed-cell foam neoprene, metalized film, opacified molded polymer.
In certain embodiments, in order to contribute to guaranteeing that the light near the guard shield of experimental subject seals, be first placed on above experimental subject by opaque drop cloth, this drop cloth has opening, it can not be covered and change area-of-interest.Can contact around this area-of-interest with this drop cloth after the lower limb of guard shield.
Not rely on the guard shield abutted against on drop cloth, preferably sealing device is set, to be fixed on drop cloth by guard shield.Sealing device can be, such as, and physics (such as Velcro
tM), magnetic, vacuum or electrostatic sealing member.Alternatively, guard shield and sealing member are by adapter as stiffening ring physical connection each other, and this stiffening ring is connected by guard shield and drop cloth.External power source such as vacuum line is alternatively used to be connected sealing.
In guard shield, be provided with optical sensor in certain embodiments, this optical sensor can be used for being confirmed whether to establish light closed chamber.In other are implemented, can carry out confirming (this imaging device may be used for collecting illuminated picture picture especially as discussed below) with the image gathered by imaging device.
This imaging device can be charge-coupled image sensor (CCD) camera.Cool electronic multiplication CCD (EMCCD) camera is preferred for the CLI image obtaining low light level.Possible optional imaging device comprises the enhancement mode CCD being collected electronics by one or more electrode, photon multiplier tube (PMT) array or microchannel plate.
When using EMCCD camera by the imaging of Cherenkov's photon, EM gain is set as at least 100 usually, preferably at least 200, more preferably from about 300.Higher EM gain can be used.Such as, for photon counting, the gain of nearly 1000 can be used.When obtaining Cherenkov's image, EMCCD camera will be cooled, and usually be cooled to-80 DEG C to-100 DEG C.
In certain embodiments, Cherenkov's imaging device (as EMCCD camera) is arranged in radiation shield, to help the interference avoiding unnecessary radiation interference such as gamma-rays or beta-particle.The form of the shielding be applicable to comprises such as lead screen and fills out the high density polyethylene (HDPE) of boron.Also other material or composite structure that can stop undesired radiation can be used.
Fibrescope comprises the lens being arranged on light guide far-end, and this light guide is used for optical signal to be sent to this imaging device from lens.The normally coherent fibre bundle of this light guide, lens are arranged on its far-end.Fibrescope can have traditional structure, and is generally flexible, easily handles this fibrescope to allow operator.The diameter of lens can be about 1.5cm.In certain embodiments, the focus of these lens can change.The adjustment of preferred lens focus is electronic, thus can provide control outside guard shield, to be conducive to lens focus when this guard shield is positioned at above area-of-interest.
In certain embodiments, the fibre bundle (or complete fibrescope) in fibrescope is shielded by radiation shield.With the shield type of imaging device seemingly, this is to help avoid unnecessary radiation interference, such as, gamma-rays in the glass fibre of described fibrescope, or the interference of beta-particle.Suitable flexible radiation shielding material comprises, such as, and the elastomer of impregnating metal.
In many cases, the illumination image (such as White-light image) of area-of-interest checked by the light closed chamber that the operator contributing to device can be formed by guard shield before Cherenkov's image acquisition and/or in the process obtained by this.
Before Cherenkov's image acquisition, this may be useful, such as, for the correct focusing of the correct location and lens of guaranteeing fibrescope.Between Harvest time, be conducive to monitoring the sequence that move and/or provide illumination sequence and Cherenkov image of fibrescope relative to area-of-interest, Cherenkov's image can overlap each other, such as to guarantee the correct registration of Cherenkov's image of order.In certain embodiments, this registration particular importance of image, such as, in the embodiment arrested by the people of easily movement at fibrescope.And if Cherenkov's image is divided into multiple frame frame subsequently usually in equal size do not have spatial registration each other, then have the loss of resolution.Fibrescope can identify at the registration carrying out illumination image and the Cherenkov's frame revised with suitable image processing program (such as, using image processing software) relative to any change in location of area-of-interest.
In some cases, surgeon also wants illumination image thus they can use the instrument in guard shield to carry out perform the operation (as cutting tissue).Particularly use the pre-Cherenkov of illumination image to gather with the tram of guaranteeing fibre scope, or when providing visible area-of-interest to carry out performing the operation to surgeon, image can be suitably video image.
In order to obtain illumination image in this guard shield, be necessary the inside illuminating the light closed chamber formed by this guard shield.The method preferably illuminating light closed chamber is in fibrescope, adopt independent illumination channel, the light of light source (such as, white light source or R/G/B light source, it can be one or more LED) far-end can be sent to from the near-end of fibrescope by this illumination channel, to provide light source at the end of this guard shield intrinsic fiber mirror.Alternately, in guard shield, such as, at the far-end of fibre scope, one or more LED can be installed.
Imagination operator switch this device between illumination and Cherenkov's imaging pattern.Some embodiments can comprise for while illumination image catch and the 3rd pattern of CLI.
Want alternating with each other at multiple illumination and Cherenkov's image and carry out (i.e. time multiplexing) in the embodiment gathered, be necessary " closedown " white light/rgb light during the cycle of CLI collection.Lamp is preferentially turned off (as LED) by reality, and mechanical shutter is used between CLI Harvest time and covers light source, and exposes light source between illumination image Harvest time.The advantage of this method is nearprompt by " lamp closedown ", avoids once no power needs to spend a period of time to stop luminous problem.
Mechanical shutter will be synchronous with described respective image acquisitions sequences.This shutter can be, such as, rotating disk, this rotating disk has the otch of aturegularaintervals at circumference, can cover to make this rotating disk off and on and expose light source.The rotation of rotating disk can be controlled to provide the light and shade period required in guard shield, can be synchronous with these these illuminations of light and shade period and Cherenkov's image acquisition.Wherein, independently photographing unit is respectively used to illumination image collection and CLI, and mechanical shutter also may be used for CLI imaging device (damaging imaging device during avoiding illumination image collection period).The shutter of CLI imaging device is can be also rotating disk.Expediently, can arrange CLI imaging device and the light source for illuminating this room makes single rotating disk can as the shutter of imaging device and light source.
In the time-multiplexed period that such illumination image and CLI gather, the persistent period of usual CLI collection period is greater than the persistent period of irradiating image acquisition period, to catch Cherenkov's image of lower intensity levels if having time.CLI collection period can be the several times of illumination period, such as the time of about 3 to 20 times.Such as, for the illumination video frequency of a 10Hz, illumination period will be 17 milliseconds, and it is 75 milliseconds that the CLI between frame gathers.Because shutter transit time in each cycle loses 8 milliseconds.When shutter close and not in the transition period time, just can enable CLI imaging.
In certain embodiments, it is not start immediately after light " closedown " (as covered by shutter) that CLI gathers, the time distributed with the light being given in any remnants in room.
In certain embodiments, may wish the imaging device that employing two is independent, one for catching illumination image with another for catching CLI image.In other embodiments, single imaging device catches two images.
When using single imaging device, usually wish imaging device to be switched between illumination level image model and low light level image model, to catch illumination image and CLI image respectively.If this is because illumination image uses the setting of identical sensitivity, those enough sensitive photographing units with the type detecting Cherenkov's photon damage possibly.When using single camera, the light level of illumination image is preferably low, and can such as by using the pulse width modulation of neutral density filter and LED to realize.
Such as, when EMCCD camera, when it is set to the relative high level for CLI by significantly cooling and EM gain, camera operates in conventional CCD mode usually, when seizure illuminated picture as time, there is no EM gain.In addition, in order to avoid ghost image, be necessary sensor is cooled down on the temperature of sensor is brought up to ambient temperature before CLI image once.
Therefore, in some embodiments of the invention, imaging device switches in the course of the work between operator scheme (Cherenkov's image capture mode and illumination image trap mode), when device switches back and forth between Cherenkov's picture catching and illumination image catch, this switching is synchronous with the opening and closing (such as, passing through mechanical shutter) of light in the chamber.
Particularly when this device is when intra-operative is for removing abnormal structure, Edge detected, the surface particularly detecting open area-of-interest is important (as mentioned above).Inventor has realized that sensitivity is reduced by the charged particle of overflowing on the surface of tissue and therefore stops producing Cherenkov's photon.The sensitivity of CLI can, by placing Cerenkov radiation body on the surface of the tissue to increase, make the charged particle of overflowing produce Cherenkov light.Cerenkov radiation body should have high index of refraction (1.5<RI<2.4), the high transmission rates of short wavelength's (<500 nanometer), and enough thin the scattering of charged particle to be minimized.
Therefore, in certain embodiments, propose use and have the Cerenkov radiation body pointed out above, this Cerenkov radiation body comprises coverslip or net.This Cerenkov radiation body can be placed on tissue surface in the region of interest.The charged particle of tissue surface and coverslip or net to interact and produce Cherenkov's photon and/or scintillation photons, this Cherenkov's photon and/or scintillation photons can carry out imaging by imaging device subsequently.
The suitable high-index material of coverslip or net comprises lead glass, zirconium glass, or tellurate glass.Net is favourable, because it can meet difform tissue surface better.Net can such as adopt the discrete portions of the high-index material such as polyurethane kept together by flexible mesh to be formed.
In certain embodiments, in order to keep aseptic, fibrescope is contained in sterile board.This case can be connected with guard shield.In one embodiment, sterile board is made up of flexible material (such as, silica gel), has transparent window (such as, being made up of glass) at far-end.In another embodiment, described sterile board is made up of hard material (such as, metal), has transparent window at far-end, and this case is can sterilizing (such as, by autoclave or ethylene oxide gas).
In second aspect, the invention provides the method for the optical imagery carrying out Cherenkov's luminescence after a kind of experimental subject accepts potion radiopharmaceutical from the area-of-interest experimental subject, the method comprises:
Area-of-interest is covered, to form light closed chamber on the region of interest with guard shield; And
Use fibrescope to catch Cherenkov's luminescent image of area-of-interest, this microscope has far-end in this guard shield and the near-end be connected with imaging device outside this guard shield.
In certain embodiments, the method also comprises the illuminated picture picture used up and illuminate this guard shield inside and catch area-of-interest when sealing chamber inside is illuminated time, catches Cherenkov's luminescent image when sealing chamber inside is not illuminated.
The method can adopt the device of first aspect above, comprise discussed above any one or multiple its preferably with optional feature.
In certain embodiments, this experimental subject can be that main body is as carried out the patient of clinical operation (such as surgical operation).
In other embodiments, experimental subject is sample or specimen.In this case, guard shield can be, such as on desktop or pallet, (such as, surgical tray) keeps the flexible light closed shield cover of sample.
Alternatively, this guard shield also can be light sealed container, such as specimen disc, and this specimen disc comprises the lid with light tight wall, with the inside stoping surround lighting to enter container.Easily, this container can be disposable.The far-end of fibre scope such as can be exposed to the inside of container by the sealed open in the wall of chamber wall or container cover.
3rd aspect of the present invention provides the method for the optical imagery after a kind of experimental subject accepts potion radiopharmaceutical, experimental subject being carried out to Cherenkov's luminescence, and the method comprising the steps of:
Catch the first image of experimental subject;
Catch the second image of Cherenkov's luminescence; And
By two image overlay.
A fourth aspect of the present invention provides a kind of device performing the third aspect.
Preferably, this first and second image comprises a series of images (as video).
Preferably, repeat the step of this seizure first image and the step of the second image successively fast, or more preferably repeat simultaneously, thus with this overlap or superposition image creation video.The video rate of the first and second images can be significantly different, and such as semi-static CLI image is 0.2Hz, and dynamic White-light image is 10Hz.
A fifth aspect of the present invention provides the method for the optical imagery after a kind of experimental subject accepts potion radiopharmaceutical, experimental subject being carried out to Cherenkov's luminescence, and the method comprising the steps of:
With the illumination of predetermined wavelength range this experimental subject bright;
The first image is caught with the first imaging device; And
Catch the second image with the second imaging device, this second image catches with the wavelength different from the wavelength of illumination light.
Preferably, method of the present invention comprises and places light shield or opaque drop cloth to cover the region of wanting imaging.Like this, the illumination disturbing operating room is not needed.
Preferably, the method comprises and uses photodetector and indicator to determine the light level in this guard shield or opaque drop cloth.This can check that operative site is fully shrouded to perform CLI.
Preferably, the method comprises that apply gating or that spectral separation is thrown light on step.Preferably, this gating or spectral separation illumination can be applicable in guard shield or drop cloth.This gating or spectral separation illumination available rooms in light source applications.
A sixth aspect of the present invention provide a kind of experimental subject accept potion radiopharmaceutical after experimental subject carried out to the device of the optical imagery of Cherenkov's luminescence, this device comprises: for catching the first imaging device of the first image; And for catching the second imaging device of the second image; Wherein this second image wavelength different from the wavelength of illumination light catches.
Preferably, described first imaging device carries out imaging to the wavelength can seeing infra-red range to experimental subject with from ultraviolet.
Preferably, two images from the first imaging device and the second imaging device are applied, to produce such as by the single image carrying out operating surgeon's use, to remove the cancerous tissue receiving radiopharmaceutical agent.
Again, preferably repeat the step of seizure first image and the step of the second image successively fast, or more preferably repeat simultaneously, thus with this overlap or superposition image creation video.
Preferably, experimental subject is only used in irradiating as the light from monochromatic HONGGUANG or blue LED illumination of spectrum red end.Preferably, experimental subject is only used in 500-740 nanometer range and preferably irradiates in 625-740 nanometer range or at the light of 435-500 nanometer range.It will be appreciated by those skilled in the art that the light of other predetermined wavelength ranges can be used for illuminating object, such as HONGGUANG, or the light of discontinuous scope (such as, Red and blue light).This is conducive to throwing light on to this experimental subject, can operate to allow such as surgeon to experimental subject.
Red illumination is better than blue illumination, because the autofluorescence that green glow can bring out in visible-range to purple light.
Preferably, this second imaging device carries out Cherenkov's luminescence imaging, to perform CLI.Preferably, this second imaging device is overdelicate and is optimized, with the CLI performed.Such as, preferably, the second imaging device is cooled to eliminate background noise (being commonly called " dark noise ").Preferably, this first and second image is calibrated.
Preferably, the light path of two imaging devices of supply is through beam splitter, thus they carry out imaging to the same area of experimental subject.Beam splitter is preferably colour splitting prism.
Preferably this second imaging device has band filter, to stop any residual light and to help to select discrete with wavelength that the is different light for imaging.The performance of beam splitter can be depended on the need of band filter.This light source also can use filter, to be minimized by spectra overlapping further.
It will be understood by those of skill in the art that this first and second imaging device can be contained in identical device.Preferably imaging device is camera.It will be understood by those of skill in the art that imaging device can be included in the charge coupled device (CCD) in photographing unit.First imaging device and the second imaging device can be included in the different CCD of in same unit two.Preferred use two imaging devices, because it allows for spectral response and dynamic range that each image selects separately.In addition, the strong illumination of sensitive camera a period of time after illumination adds dark noise.The CCD of Cherenkov's camera can have high quantum efficiency near infrared range.This chip can comprise, and such as, is collected the electron multiplication CCD of electronics, enhancement mode CCD, photon multiplier tube (PMT) array, or microchannel plate by one or more electrode.
Preferably, the second camera head is arranged in radiation shield (such as, lead screen or fill boron high density polyethylene (HDPE)), to stop the interference of unnecessary radiation interference such as gamma-rays or beta-particle.
Preferably, the plane (such as CCD) of the imaging device in the second imaging device also can be parallel to the placement of input light, to be minimized by the cross section being exposed to unnecessary radiation such as gamma-rays or beta-particle.
Preferably, image procossing is applied to two images obtained from the first and second imaging devices, with calibration intensity window and application image registration if desired.In order to further by the Iamge Segmentation from the second imaging device, additional image procossing can be performed at the image comprising spectrum and spatial information.Such as, can specify that the image of the second imaging device is only from the restricted visual field (such as operative site) in image.Another example is, the signal in pixel should meet the spectrum (as Cherenkov's spectrum) of the expectation that radiopharmaceutical agent is launched.
Preferably, placement light shield or opaque drop cloth want the region of imaging with shielding.Like this, without the need to the illumination of interference in operating room, this is in case of emergency favourable.
Preferably, photodetector and indicator may be used for checking that this wants the region of imaging (such as, clinical location) fully to be shrouded to perform CLI.
A seventh aspect of the present invention provide a kind of experimental subject accept potion radiopharmaceutical after experimental subject carried out to the method for the optical imagery of Cherenkov's luminescence, the method comprising the steps of:
With the illumination of light source this experimental subject bright;
The first image is caught when experimental subject is bright by the illumination of light source time; And
The second image is caught when experimental subject is not bright by the illumination of light source time.
In a seventh aspect of the present invention, the preferred area-of-interest most of the time is penetrated by the illumination of light source.The light of preferred light source is launched in repetition pulse.Preferred flash lamp illumination should be greater than 100Hz and the pulse duration should be 10-1000 microsecond.Usually the surgeon such as operated experimental subject is imperceptiblely greater than the flash lamp illumination of 100Hz.When the illumination of experimental subject light source is penetrated, obtain the first image of experimental subject, or obtain a series of first image.Then, the short time interval between the pulse of illumination, light source is closed, and experimental subject is not penetrated by the illumination of light source.Preferably, at this moment in interval, experimental subject place in the dark.During this period, the second image can be obtained, or obtain a series of second image.Second image can detect Cherenkov's luminescence during this period.This order can repeat, the photoimaging of generation light source and do not have repetition or the pulse of carrying out Cherenkov's imaging during the light of light source.Afterwards preferably, the first and second images or image sequence, superimposed or superposition.Preferably, to overlap or the video of the first and second image sequences that superposes.
A eighth aspect of the present invention provides the device of the optical imagery after a kind of experimental subject accepts potion radiopharmaceutical, experimental subject being carried out to Cherenkov's luminescence, and this device comprises: for catching the first imaging device of the first image of experimental subject; And for the second imaging device of the second image of catching experimental subject; Wherein this first and second imaging device is connected with stroboscopic illumination device, and this second image catches when this experimental subject is not illuminated by this stroboscopic illumination device.
Preferably, described first image the first imaging device acquisition and the second image the second camera head obtains.But be understandable that, the first and second images can obtain with identical imaging device.This is very important, because the imaging device being suitable for these application is expensive, can reduce costs like this.
Time migration preferably between gate pulse and collection the second image or strobe offset long enough, to allow the decay of the tissue autofluorescence of any induction, and allow to remove any electric charge at imaging device (such as CCD).
Preferably the signal from illuminator is cut off in the collection of the second image.Such as digital micro-mirror device (DMD), liquid crystal shutter or spatial light modulator can be used to perform gated acquisition.
Optimization experiment object is illuminated by automatic stroboscopic illumination.It is further preferred that stroboscopic illumination is automatically, such as, the white-light illuminating with grid-control shutter of Pockers cell or digital micro-mirror device (DMD) is used.
Preferably the first image is structural images and the second image is Cherenkov's image.When structure and Cherenkov's image be measured by identical imaging device, gated acquisition can by performing the fragment of this signal as Cherenkov's image.
Preferably, the plane (such as CCD) of imaging device, also can be parallel to input light and place, to be minimized by the cross section being exposed to unnecessary radiation such as gamma-rays or beta-particle.
Preferably, the first and second images are calibrated.Preferably, if needed, image procossing is carried out to the first and second images, to calibrate brightness window and application image registration.In order to split image further, the image procossing that the image that can comprise spectrum and spatial information to this adds.Such as, the spectrum (as Cherenkov's spectrum) of the expectation that radiopharmaceutical agent is launched should can be met by the signal in determined pixel.
If use two imaging devices, preferably, this second imaging device is overdelicate and is optimized, to perform CLI.Such as, preferably, the second imaging device is the electron multiplication CCD camera of cooling.
Preferably, the light path of two imaging devices of supply is through beam splitter, thus they carry out imaging to the same area of experimental subject.Beam splitter is preferably colour splitting prism.
Preferably this second imaging device has band filter, to stop any residual light and to help to select discrete with wavelength that the is different light for imaging.The performance of beam splitter can be depended on the need of band filter.
It will be understood by those of skill in the art that this first and second imaging device can be contained in identical device.Preferably imaging device is camera.It will be understood by those of skill in the art that imaging device can be included in the charge coupled device (CCD) in photographing unit.First imaging device and the second imaging device can be included in the different CCD of in same unit two.Preferred use two imaging devices, because it allows for spectral response and dynamic range that each image selects separately.The CCD of Cherenkov's camera can have high quantum efficiency near infrared range.This chip can comprise, and such as, is collected the electron multiplication CCD of electronics, enhancement mode CCD, photon multiplier tube (PMT) array, or microchannel plate by one or more electrode.
Preferably, the second camera head is arranged in radiation shield (such as, lead screen or fill boron high density polyethylene (HDPE)), to stop the interference of unnecessary radiation interference such as gamma-rays or beta-particle.
Preferred above-mentioned aspect also can be applied to other diagnosing image method as endoscope, capsule type endoscope, robotic surgery imaging, whole body imaging, and basic research.
Another aspect of the invention provides a kind of mirage for superweak light or test copy.Mirage can use light emitting diode (LED), and this light emitting diode has one or more such as neutral density filters heap or layer, and the light of LED is piled by this neutral density filters or layer injection.Alternatively or in addition, wavelength chooses attenuator can be used in the led.The minimizing of intensity can alternatively, or in addition use pulse width modulation to realize, and pulse width modulation can use electronics or software engineering to change.Mirage may be used for alignment light system, and also can or alternately be conducive to safeguarding and/or Mass Control.
Accompanying drawing explanation
Now by reference to the accompanying drawings embodiment is described, wherein:
Fig. 1 illustrates the embodiment of example of the present invention;
Fig. 2 illustrates that the present invention uses the embodiment of the example of stroboscopic illumination;
Fig. 3 illustrates the stroboscopic illumination of the embodiment of example of the present invention, the sequence that the image (such as, anatomic image) of Cherenkov's image acquisition and light structures gathers;
Fig. 4 a show schematically show the embodiment of use for the fibrescope of Cherenkov's luminescence imaging of a first aspect of the present invention;
Fig. 4 b to 4d illustrates the change of the guard apparatus of the fibrescope embodiment for Fig. 4 a;
Fig. 5 diagrammatically illustrates employing two photographing units and by the optical coupler of photoconduction to two video cameras and the alternate embodiment of shutter;
Fig. 6 a and 6b illustrates two optional settings for the photo-coupler in the embodiment of Fig. 5;
Fig. 7 a shows the cross section that top view and Fig. 7 b show shutter rotating disc, and this shutter rotating disc can be used for covering light source and EMCCD camera;
Fig. 8 uses in an experiment, the schematic diagram arranged with optics shading and camera that the principle of the embodiment of the present invention is described;
Fig. 9 shows the layout of the sample well used in an experiment;
Figure 10 a and 10b shows the Cherenkov's image caught in experimentation; And
Figure 11 is the curve chart of the signal photon velocity of each experiment well.
Detailed description of the invention
Example embodiment of the present invention as shown in Figure 1.This example embodiment allows to carry out CLI under bright condition.In this example embodiment, background illumination is completely eliminated, and the illumination of monochromatic red-light LED is used for illuminating experimental subject.The exemplary setting of camera and other elements of imaging system also can be used for the environment of conventional ambient lighting, want the experimental subject of imaging to be shrouded to get rid of surround lighting in this context, make further discussion below.
In this example embodiment, experimental subject is injected
18f-fluorodeoxyglucose (FDG) (common β launches radiopharmaceutical).Radiopharmaceutical can whole body or local injection.Usually, there is the narrow time window of about 60 minutes to 3 hours being used for the scanning that will perform.This is pharmacokinetics and the radiopharmaceutical result at area-of-interest radioactive decay.
Two independent video cameras (C1 and C2) are respectively used to illumination image and Cherenkov's image.Use two independent cameras can select spectral response and dynamic range respectively for each image.Second camera (C2) is that a kind of hypersensitive photographing unit such as cools EMCCD camera.For first camera (C1), one or more monochrome or color camera can be used.Red by applying (with any order) continuous print fast, green and blue illumination then composograph, can provide full color imaging.The speed that illumination applies is determined by the expectation frame rate of video image.
In alternative embodiments, low-down horizontal illuminance and single camera is used to can be used for utilizing the sensitivity of CLI camera.If the coloured image needed, this illumination can be HONGGUANG, green glow and the blue light of flicker.
First-selection has the large aperture camera lens of low f number.This device means can collect more light.Usually do not wish like this, because can distortion be caused.But spatial resolution is fully kept for CLI, CLI has poor spatial resolution usually, thus the improvement of light input is wanted than the weight losses of spatial resolution.
The light that radiopharmaceutical produces is by beam splitter (BS) as colour splitting prism, and HONGGUANG is directed to described first camera and non-HONGGUANG is directed to second camera by this colour splitting prism.Second camera is also equipped with band filter (BP), to stop the red light of any remnants.The performance of beam splitter will be depended on the need of band filter.Red and blue effect can be put upside down, and to allow, such as, surgeon can see darker tissue, a part for light is directed to illumination photographing unit and a part for light is directed to Cherenkov's photographing unit.
C2 is also enclosed in radiation shield (such as, lead screen) (RS), to stop any interference of gamma ray or beta particle.The plane of C2 camera chip also can be parallel to input light, to be minimized by the cross section being exposed to gamma ray or beta particle.
If necessary, image procossing (P) is applied to two images (I1 and I2) and comes calibration intensity window and application image registration.In order to split Cherenkov's image further, additional imaging processing can be performed to the I2 comprising spectrum and spatial information.Such as, the restricted visual field (tumor as surgical site in) of Cherenkov's image only from the beginning in I2 can be specified.Another example is, the signal in pixel should meet Cherenkov's spectrum of expection.Final image (I) produces by the illumination image (I1) that is added to by Cherenkov's image (I2) is upper.
In another embodiment of the present invention, CLI can be performed in the interval between the stroboscopic pulse of light.In this example embodiment, experimental subject is illuminated by automatic stroboscopic illumination.In the present embodiment, illumination is white-light illuminating, and white-light illuminating has the gate shutter of use digital micro-mirror device (DMD).The shutter of other method within the scope of the invention.In certain embodiments, the illumination of stroboscopic or spectral separation can be provided in light shield.In certain embodiments, the illumination of stroboscopic or spectral separation can be provided in a room.
Employ the device being similar to above-described embodiment in the present embodiment to arrange.In this example embodiment, the signal of stroboscopic illumination system is cut off in the collection of the second image, as shown in Figure 2.Digital micro-mirror device (DMD) is used to carry out gated acquisition.In the embodiment using stroboscopic illumination, DMD is connected to light source by trigger (TR).Connect light source and DMD by trigger, two cameras that light can be allowed to be directed into are to carry out independent Cherenkov's image or the imaging of structural images.
Fig. 3 shows the stroboscopic pulse of example and the sequence at interval.In an example embodiment, flash lamp illumination can be greater than 100 hertz, and the pulse duration (PD) can be 10-1000 microsecond in an example embodiment.In stroboscopic pulse duration performing structure image acquisition.In this example embodiment, the time between gate pulse and collection the second image or strobe offset (GO) long enough, to allow the decay of the tissue autofluorescence of any induction, also allow to remove any electric charge at camera C CD simultaneously.In the exemplary embodiment, if the pulse duration (PD) is 1000 microseconds, pulse spacing (PI) is 9000 microseconds, so strobe offset (GO) can be 2000 microseconds and second (Cherenkov) image acquisition time is 7000 microseconds.In another example embodiment, if the pulse duration (PD) is 10 microseconds, pulse spacing (PI) is 9990 microseconds, so strobe offset (GO) can be 1990 microseconds and second (Cherenkov) image acquisition time is 8000 microseconds.
In some embodiments, light shield can be used for shielding patient, or wants the region of imaging.Light shield is guard shield or the shielding that substantially can prevent surround lighting transmission cover material, makes the lamp without the need to closing room and can carry out CLI measurement.Alternatively, this light shield can meet required shape.Alternatively, this light shield is by the material of profile of health that can meet such as patient.Guard shield can comprise fabric or metal forming, and anticipation reaches other material of desired effect.Guard shield can make the surface optical of patient seal.Optical encapsulant can realize with such as gel.Described gel can around the edge of guard shield and contact patients.Wavelength " passband " light level in guard shield should be reduced to by guard shield can level compared with CLI signal, even than the level of lower CLI signal.
Alternatively, this guard shield can comprise built-in glove, and to allow, such as, surgeon does not destroy optical encapsulant close to area-of-interest during imaging.Alternatively or in addition, apparatus port and/or apparatus can be comprised.
Alternatively or in addition, image display can be carried out at camera.
In certain embodiments, flexible pier or endoscope may be used for Cherenkov's luminescence imaging.
Fig. 4 schematically shows the embodiment of a first aspect of the present invention, and fibrescope 10 is for carrying out imaging at the tissue (such as operative site) of the intra-operative carried out patient 14 to area-of-interest 18 in this embodiment.
As shown in Figure 4, fibrescope 10, it is preferably flexible, is easy to surgeon and uses, extend to the area-of-interest 18 patient 14 from electron multiplying charge couple device camera (EMCCD) 12.It is envisaged that, fibrescope 10 with hand-held, but can provide physical support by surgeon or assistant in other example.The end 16 of fibrescope 10 is for carrying out imaging to the tissue at area-of-interest 18.
EMCCD camera is supported by suspension rod 20.
Light shield 22 (or opaque drop cloth) around the far-end 16 of fibre scope 10 and area-of-interest 18, make light shield 22 seldom inner or there is no an exterior light and the light of outside be prevented from entering interested region 18.Preferably, light shield 22 is arranged on the end of fibrescope 10.Can to provide the sealing of light shield 22 such as near patient to seal with identical mode above.The alternative method realizing sealing around the light at the edge of guard shield is discussed below with reference to Fig. 5 b to 5d.This guard shield also seals near fibrescope.
Alternatively, the shirt rim of drop cloth 24 can be used for spreading all over the patient 14 away from area-of-interest 18.Shirt rim 24 can be connected with guard shield 22, to help to stop light to enter area-of-interest 18.
Such as, as shown in Figure 4 b, drop cloth can be connected with the lower limb of stiffening ring and the guard shield formed with clasp, and this shell can form light seal along engage with the upper of ring.The anti-stop ring of sponge member below ring compresses into the skin of patient, is also conducive to guaranteeing that the light maintained near skin seals.
Fig. 4 c and 4d shows the alternative setting for guard shield being sealed to drop cloth.At Fig. 4 c, this guard shield is connected on the upper surface of drop cloth by sealing member, and the seal can be, such as hook and annular seal, magnetic seal or electrostatic sealing member.In the present embodiment, fibrescope extends into guard shield by light sealed port.
In the example shown in Fig. 4 d, the foundation of sealing does not use any physical connection but relies on the overlap of the length between guard shield shirt rim and drop cloth to realize.In the present embodiment, sponge member is also for strengthening sealing.
Can by the one or more glove through this optical cover 22, through the line of this optical cover 22, or the end 16 of rigid end to fibrescope 10 arranging fibrescope 10 at end 16 is handled, thus can from the manipulation outside end 16 of guard shield 22.The alternate manner handling the end 16 of fibrescope 10 it will be apparent to those skilled in the art that.
Usually with the naked eye whether optical encapsulant is formed hardly.Therefore, in certain embodiments, photodetector and indicator may be used for providing feedback to such as surgeon, to provide the light sealing information about this light shield.In certain embodiments, photodetector is camera.In certain embodiments, photodetector can be CLI camera.Additional detector can be used, to prevent such as illuminance too large damage CLI camera.
Fig. 5 shows alternate embodiment.In the present embodiment, imaging device comprises two cameras, for the EMCCD camera of CLI and the color video camera for illumination (such as dissecting) imaging.Also shown is the white light source of the near-end at fibrescope, what this white light source can be used for illuminating patient is shrouded region.Photo-coupler and fast goalkeeper are solely directed to two cameras and shutter is EMCCD camera during the inside of guard shield is illuminated.Shutter is controlled by shutter controller with synchronous with illumination.
Fig. 6 a shows the exemplary setting of optical coupler and shutter.In the present embodiment, single non-spherical lens is for being coupled fibre bundle focus on two cameras.Show high transmitted light beam separator option.
Fig. 6 b shows the selection of the setting of another kind of optical coupler.In the present embodiment, modular setting uses together with being connected to the condenser lens of each photographing unit with the collimating lens of coupling fibre bundle.This embodiment also shows high transmitted light beam separator option.
Fig. 7 a and 7b shows alternative shutter and arranges, and this shutter arranges and can be used for covering in the embodiment of light source and EMCCD camera, wherein light source and camera adjacent one another are.Shutter is set to the rotating disk covering light source and EMCCD lens.When this dish is driven by motor and rotates, the window (hole) of dish aligns from described light source and described EMCCD lens (their radiuses are different) respectively, means that light source and EMCCD camera lens are optionally covered and expose.The relative position of these windows guarantees that EMCCD lens are capped when light source exposes.Best seen in Fig. 7 a, EMCCD window is longer than light source window, thus CLI collection period is long according to bright image acquisition period.
Fig. 8 shows the schematic diagram of exemplary optics shading of the present invention and camera setting, and this setting is used for experiment discussed below.In this example, iXON camera is arranged on wanting directly over Imaged samples (not shown) on metal mounting disc b.F/1.8 camera lens C is positioned at below camera and metal mounting plate B.Plastics (PVC) pipe d extends between metal mounting plate b and the sample wanting imaging.Plastic tube d studs with low reflection cotton thread lining.Sample surrounds by packing foam f, and packaging foam coverage has neoprene foams rubber lining g, is coated with draw springs h afterwards.
In certain embodiments, for the mirage of superweak light, or test copy can be used for alignment light system.Mirage can use the light emitting diode (LED) with neutral-density filter heap or layer.If necessary, LED can drive by modulation waveform, to reduce the output of LED further and controllably.Such mirage or alternatively can be conducive to maintenance and the quality control of photosystem.
It will be apparent to one skilled in the art that it is possible for not deviating from the various amendments to specifically described embodiment of the present invention.The following example is for supporting some aspect of the present invention.
example
example 1
IXON surpasses the pole low levels that 897EMCCD camera is used for detecting CLI expection.Use and there is the LED of neutral density filter and diffusing globe carrys out analog light source.Use f/2.8 camera lens, but light level is scaled to simulate f/1 camera lens.
Target irradiation degree is 0.013 photons/pixel/second.
calibration
The number of photons that LED produces is distributed into by collimator the circular light beam that diameter is 25mm by dutycycle (LED opens the time scale of 1 second) convergent-divergent.Once be decayed by neutral density filter, light beam enters heavy diffusing globe.The random direction of each photon causes the photo emissions of half to opposite side.These photons are dispersed at 2 π SR (hemisphere) and are spread now.This provides photons/second/SR/ centimetre
2radiation, and allow the irradiance of detector to predict.
cellular rubber cover
Measure for low irradiance, OD4 with OD2 filter uses together with 1/10 dutycycle.Camera is used for photon counting mode, and photon counting mode adopts the count threshold of photon, and the impact of the unnecessary noise factor of removal, carries out digitized to each pixel.
Camera arranges as follows:
CD thermoelectric-cooled is to-80 DEG C
1MHz gain 3 enlarge leadingly
1000 times of EM gains
The image (32 × 32 combination of pixels) of 16 × 16
Photon counting threshold value=500
F/2.8 camera lens
0.5 μ s translational speed
The lamp in room is closed, and the signal exposed 1 second is 0.0048 photons/pixel.This corresponds to the S:N of 1.7 of 32 × 32 combination of pixels.
Lower than expection photon counting can owing to the photon counting threshold value used and because the scattered light that leaks of light source to do little of background but (now) contribute significantly, make this signal factitious little.
May be because guard shield is to the little gap of surface interface, the lamp turning on room causes background higher 25 times than the signal level detected from source.
Measure the dutycycle of employing 1/2 and 1/5.
Put it briefly, the lamp in room extinguishes can measurement target irradiance.Photon counting needs very high gain and is not very effective.Cellular rubber cover is good at stopping light.Found that folding and create the gap entered at the light that the permission be combined with large periphery at interface is too many, measuring time bright with compartment lamp.
Silica gel cone-shaped shield
OD4 with OD2 filter uses together with 1/10 dutycycle.
CCD thermoelectric-cooled is to-80 DEG C
1MHz gain 3 enlarge leadingly
300 times of EM gains
The image (32 × 32 combination of pixels) of 16 × 16
F/2.8 camera lens
0.5 μ s translational speed
The lamp in room is closed, and the signal exposed 1 second is 0.0015 photons/pixel.This corresponds to the S:N of 2.1 of 32 × 32 combination of pixels.
Due to the scattering of environment photon, open background light and create not corresponding with described source signal.Bright 5 times of the image ratio source radiation in source, and can not source be measured when therefore compartment lamp is opened.
Compartment lamp is closed, and (can use the dutycycle of 1 to 100) and measure the radiation of low 10 times.For the measurement of 10 seconds, signal level was 0.019 photons/pixel, obtained the S:N of 2.1.
In brief, compartment lamp is closed, can measurement target illumination.Use the exposure time of 10 double-lengths can measure the radiation of low 10 times.Silica gel cone-shaped shield provides the sealing of good quality on flat surfaces, but does not have enough light tight and allow optical transport to blind zone.
Cellular rubber and conical silicon guard shield combine
Described OD4 with OD2 light filter uses together with 1.100 dutycycles with 1.10.Camera arranges as follows:
CCD thermoelectric-cooled is to-80 DEG C
1MHz gain 3 enlarge leadingly
300 times of EM gains or 100 times of EM gains
The image (32 × 32 combination of pixels) of 16 × 16
F/2.8 camera lens
0.5 μ s translational speed
The lamp in room is opened, and the signal exposed 1 second is 0.0015 photons/pixel, corresponding to the S:N of 1.7 of 32 × 32 combination of pixels.
Extra measurement is carried out with the irradiance of low 10 times and 100 times of EM gains.Some of them are shown in following table.
| Source dutycycle | EM gain | The time of integration | Signal (photons/pixel) | S:N | Amplify |
| 1/10 | 100 | 1 | 0.015 | 2.2 | 0.246 |
| 1/10 | 300 | 1 | 0.016 | 3.1 | 0.246 |
| 1/100 | 100 | 10 | 0.017 | 2.4 | 0.246 |
| 1/100 | 300 | 10 | 0.016 | 1.9 | 0.246 |
In brief, compartment lamp is opened, and uses the EM gain of 100 times can measurement target illumination.
Therefore, can reach a conclusion, use suitable guard shield, as outer circumference has the silica gel circular cone of cellular rubber layer, can be used for shielding surround lighting and open to the lamp reaching room the level can carrying out CLI.
example 2
The in-vitro measurements iXON of the Cerenkov radiation that F18FDG sends surpasses 897EMCCD camera to carry out.
Camera is arranged, experiment can be carried out in lead screen, operate with the another side of computer in room.Camera has following setting:
50mm f/2.8 camera lens
CCD temperature :-80 DEG C
1MHz gain is set as the preamplifier of 3
The vertical translational speed of 0.5 μ s
300 times of EM gains
Visual field is 47 × 47mm
F8 dilutes and is distributed at Perspex
tM(PMMA) in the experiment well of 6 0.2 milliliter in block.Also the control well that three have inert matter has been prepared.Fig. 7 illustrates the layout of experiment well.
Liquid volume in active well and initial activity concentration are shown in following table.
| Active (μ Ci) | Volume (μ l) | Active concentration (nCi/ μ l) | Well is numbered |
| 2 | 200 | 10 | 4 |
| 1 | 100 | 10 | 1 |
| 0.5 | 200 | 2.5 | 1 |
Activity is that the BK7 glass that the control well of 2 μ Ci and active well 6mm are thick covers.Activity is that BK7 glass that the control well of 2 μ Ci and active well 6mm are thick and black masking tape cover.BK7 glass is insert, has the well as being watched by camera below it, and this well is lower than 6 millimeters, other wells.Black masking tape is placed between well and glass, allows glass open wide for viewing.
Prepare below camera that sample block being placed on shielded, is then reduced destination and with drop cloth covering, to obtain light closed chamber.
Need the picture with following setting:
1.1 second time of integration, resolution 16 × 16 (32 × 32 combination of pixels)
2.3 second time of integration, resolution 16 × 16 (32 × 32 combination of pixels)
3.5 second time of integration, resolution 32 × 32 (16 × 16 combination of pixels)
Shooting has the more image of identical setting, and in whole experiment, the lamp in room opens and closes at regular intervals.
After experiment, derive each image and the initial data of counting is converted to the signal of the photoelectron (or the photon detected) of formula under use:
Bias offset=200 count
Conversion coefficient=4.27 electronics/counting
EM gain=300
Result
Figure 10 a shows the image that shooting in about 15 minutes has been carried out in the experiment opened and closed with lamp.The position in hole has used in the image in the upper left corner to be irised out with the identical scheme of Fig. 6.Can find out, in 5 seconds, obtain higher resolution 32 × 32.Except Cherenkov launches, the interference of high-energy rays can be regarded as random white pixel, and this white pixel has the signal level exceeding used scale.
Figure 10 b shows the image that shooting in 180 minutes has been carried out in experiment.Although have comparatively low-signal levels, due to the cause of the lamp in room, not obvious difference.Still easily see higher active hole, minimum activity well still can be distinguished.
Figure 11 shows the signal photon rate by deducting each active sample well after corresponding control signal correcting background.The image of each expression sample on figure.The decay constant recorded corresponds to the half-life of 108 minutes.
All three control samples display no signals.The signal of open well is directly proportional to their initial activity.These mux--out signal exhibits go out to have the exponential damping of the half-life of mating with the half-life of F18FDG (110 points).Therefore, can reach a conclusion, measure at present and resulting from the Cerenkov radiation of activity of F18FDG.
The signal similar by active well that is glass-faced but that do not have covered active well to produce and open wide.Sightless signal is shown by the well covered, and 10% of the quantitative signal for obtaining from the well opened wide.Therefore can reach a conclusion, the flicker in optical glass BK7 is not remarkable.
There is the remarkable interference from gamma ray.But shield if directly impacted from gamma-rays and particle by sensor in principle, more high-resolution is possible.In addition, this may detect the activity being low to moderate 160nCi (0.8nCi/ μ l), and the spatial resolution of this activity is low to moderate 400 μm.
Claims (39)
1. experimental subject to carry out a device for the optical imagery of Cherenkov's luminescence from the area-of-interest experimental subject after accepting potion radiopharmaceutical, and this device comprises:
Imaging device, this imaging device can by the imaging of Cherenkov's photon;
Fibrescope, this fibrescope is used for the optical transport that received by the far-end at the fibrescope near-end to fibrescope, and the near-end of fibrescope is connected with imaging device; And
Light shield, this light shield for surround fibrescope far-end and for covering area-of-interest.
2. device as claimed in claim 1, also comprise opaque drop cloth, this drop cloth is placed on experimental subject, and this drop cloth has the feather edge of opening and this guard shield for being connected around this opening with this drop cloth.
3. device according to claim 2, comprises sealing device, so that this guard shield is fixed to this drop cloth.
4. device as claimed in claim 3, wherein sealing device is physics, pneumatic, hydraulic pressure, magnetic or electrostatic sealing member, or physical attachment.
5. the device as described in any one in aforementioned claim, is included in the optical sensor in this guard shield.
6. the device as described in any one in aforementioned claim, wherein the adjustment of this fibrescope lens and lens focus of being included in far-end is electronic.
7. the device as described in any one in aforementioned claim, comprises the radiation shield for the fibre bundle in fibrescope or complete fibrescope.
8. the device as described in any one in aforementioned claim, is included in the illumination channel in fibrescope, and the light of light source can be transferred to the far-end of fibrescope from the near-end of fibrescope by this illumination channel, to provide light source at the end of guard shield intrinsic fiber mirror.
9. the device as described in any one of claim 1-7, comprises one or more light source be contained in guard shield.
10. device as claimed in claim 8 or 9, comprise mechanical shutter, to cover this light source between CLI Harvest time, and expose this light source between illumination image Harvest time, wherein this mechanical shutter is synchronous with respective image acquisitions sequences.
11. devices as described in any one of claim 8-11, wherein this device is controlled, and makes the persistent period of CLI collection period be greater than illumination image collection period.
12. devices as described in any one in aforementioned claim, comprise Cerenkov radiation body, this Cerenkov radiation body can be placed on the tissue surface of area-of-interest.
13. devices as described in any one in aforementioned claim, wherein fibrescope is contained in inside sterile board.
14. 1 kinds of experimental subjecies to carry out the method for the optical imagery of Cherenkov's luminescence from the area-of-interest experimental subject after accepting potion radiopharmaceutical, the method comprises:
Area-of-interest is covered, to form light closed chamber on the region of interest with guard shield; And
Use fibrescope to catch Cherenkov's luminescent image of area-of-interest, this fibrescope has far-end in this guard shield and the near-end be connected with imaging device outside this guard shield.
15. methods as claimed in claim 14, also comprise using up and illuminate this guard shield illuminated picture picture that is inner and seizure area-of-interest when sealing chamber inside is illuminated time, catch Cherenkov's luminescent image when sealing chamber inside is not illuminated.
16. methods as described in claims 14 or 15, wherein the method comprises the device used described in any one of claim 1-13.
17. 1 kinds of experimental subjecies to carry out the method for the optical imagery of Cherenkov's luminescence to experimental subject after accepting potion radiopharmaceutical, the method comprising the steps of:
Catch the first image of experimental subject;
Catch the second image of Cherenkov's luminescence; And
By two image overlay.
18. methods as claimed in claim 17, this first image is caught by the first imaging device and the second image is caught by the second imaging device.
19. methods as claimed in claim 17, this first image is caught by identical imaging device with the second image.
20. methods as described in any one of claim 17-19, wherein the illumination of experimental subject predetermined wavelength range is penetrated and this second image catches with the wavelength different from the wavelength of illumination light.
21. 1 kinds of experimental subjecies to carry out the method for the optical imagery of Cherenkov's luminescence to experimental subject after accepting potion radiopharmaceutical, the method comprising the steps of:
With the illumination of light source this experimental subject bright;
The first image is caught when experimental subject is bright by the illumination of light source time; And
The second image is caught when experimental subject is not bright by the illumination of light source time.
22. methods as claimed in claim 21, wherein this first image and the second image are applied.
23. methods as described in claim 21 or 22, wherein to detect Cherenkov luminous for this second image.
24. methods as described in any one of claim 17-23, wherein this experimental subject wavelength illumination between 500-740nm is bright.
25. methods as described in any one of claim 17-23, wherein this experimental subject wavelength illumination between 435-500nm is bright.
26. methods as described in any one of claim 17-25, comprise step: place light shield or opaque drop cloth to cover the region of wanting imaging.
27. methods as claimed in claim 26, comprise step: use photodetector and indicator to determine the light level in this light shield or opaque drop cloth.
28. methods as described in any one of claim 17-27, comprise step: application stroboscopic illumination.
29. 1 kinds of experimental subjecies to carry out the device of the optical imagery of Cherenkov's luminescence to experimental subject after accepting potion radiopharmaceutical, this device comprises:
Imaging device, this imaging device is for the second image of the first image and experimental subject that catch experimental subject, and this second image comprises the image of Cherenkov's luminescence; And
For the blood processor by two image overlay.
30. devices as claimed in claim 29, wherein this first image is caught by the second imaging device by the first imaging device seizure and this second image.
31. devices as claimed in claim 29, wherein this first image is caught by identical imaging device with the second image.
32. devices as described in any one of claim 29-31, comprising:
Illuminator, for the illumination of predetermined wavelength range this experimental subject bright; And
The device of this second image is caught with the wavelength different from the wavelength of illumination light.
33. 1 kinds of experimental subjecies to carry out the device of the optical imagery of Cherenkov's luminescence to experimental subject after accepting potion radiopharmaceutical, this device comprises:
First imaging device, for catching the first image when this experimental subject is illuminated time; And
For the second imaging device of Cherenkov's luminescence imaging, for catching the second image of experimental subject;
This second image catches when this experimental subject is not illuminated.
34. devices as claimed in claim 33, wherein this device comprises blood processor, and this blood processor is used for these two image overlay.
35. as claim 30, the device described in 32,33 or 34, and wherein this second imaging device catches Cherenkov's luminescent image.
36. devices as described in any one of claim 26-32, wherein this imaging device is contained in endoscope.
37. devices as described in any one of claim 26-33, comprise light shield or opaque drop cloth, for covering the region of wanting imaging.
38. devices as claimed in claim 34, comprise photodetector and indicator, for determining the light level in this light shield or opaque drop cloth.
39. devices as described in any one of claim 26-36, wherein this imaging device comprises monochrome cameras, and it is red that this monochrome cameras can apply continuous print with random order supper-fastly, and green and blue illumination, to provide full-colour image.
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| PCT/GB2013/052087 WO2014020359A1 (en) | 2012-08-03 | 2013-08-05 | Fibrescope for optical imaging of radiopharmaceuticals |
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| CN201380041336.6A Expired - Fee Related CN104780829B (en) | 2012-08-03 | 2013-08-05 | For the sample chamber of radiopharmaceutical optical imagery |
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| KR20150058174A (en) | 2015-05-28 |
| GB201213827D0 (en) | 2012-09-19 |
| US9816947B2 (en) | 2017-11-14 |
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| EP2879566B1 (en) | 2019-12-11 |
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| EP2879565B1 (en) | 2016-10-26 |
| KR20150054783A (en) | 2015-05-20 |
| US20150230696A1 (en) | 2015-08-20 |
| JP6325540B2 (en) | 2018-05-16 |
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